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Sequence and destroy: the quest to eliminate the last stocks of deadly rinderpest virus

Labs are being encouraged to sequence their remaining samples of the devastating livestock virus — and then get rid of them for good.

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South Africa circa 1900: Dead oxen, some partly buried, thought to have died from rinderpest.

Rinderpest killed more than 90% of cattle in sub-Saharan Africa at the turn of the twentieth century.Credit: Reinhold Thiele/Getty

Scientists who work with the deadly livestock virus rinderpest — only the second disease ever wiped out, after smallpox — achieved a milestone last month when they destroyed a huge proportion of the world’s last remaining virus samples.

But overall progress in eliminating the final laboratory stocks of the virus has proved slow. When the disease was eradicated from the wild in 2011, dozens of labs worldwide, some with poor safety standards, held the virus, which laid waste to cattle across Europe and Asia for thousands of years. Now, international authorities are renewing a push for samples of rinderpest to be either destroyed or consolidated in high-security facilities to reduce the risk of re-emergence through an accidental or deliberate release. Some labs are participating in a research programme called Sequence and Destroy, which involves sequencing the complete genomes of the various strains they hold before destroying them for good.

“The world is not out of the woods,” says Paul Fenimore, a theoretical biologist at the Los Alamos National Laboratory in New Mexico, who has modelled the potential progress of epidemics resulting from a rinderpest release. International efforts to consolidate and eliminate stocks have already greatly reduced the risk that rinderpest could return, says Fenimore. But the chance of an accidental release, although low, exists as long as lab stocks remain, he says. A recurrence could cause “billion-dollar-scale disruption at a national or regional level”, he adds.

Ref: FAO/OIE.

Feared disease

Rinderpest virus, also known as cattle plague, is in the same family as measles, but does not infect humans. It causes symptoms including fever and severe diarrhoea and dysentery in cattle, which die days after showing signs of disease. When livestock imports introduced the illness to sub-Saharan Africa in the late nineteenth century, it killed more than 90% of the cattle and oxen there. Devastating famines followed, and the events are considered Africa’s worst natural disaster.

That’s why, after eradication, the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) agreed to destroy any material containing rinderpest virus held in labs, or ship it to a handful of FAO–OIE designated high-security facilities, says Monique Eloit, director-general of the OIE in Paris. The World Health Organization launched a similar effort after smallpox was eradicated in 1980 — today, the only declared stocks are in two approved labs in the United States and Russia.

Authorities worldwide consider rinderpest one of the most dangerous agricultural bioterrorism threats — but greatest threat could be long-forgotten samples lurking in lab freezers. Fenimore points to outbreaks of foot and mouth disease in the United Kingdom in 2007, which were traced to leaks from a drainage pipe at the Pirbright Institute, an animal-health research centre in Woking, UK, as an example of how an accidental release can happen even at a world-class facility.

Progress in destroying stocks — which include samples of the live virus, the vaccine, and blood and tissue samples collected for research — was swift at first. But there has been a variable response in recent years, says John Lubroth, the FAO’s chief veterinary officer. That’s in part because the FAO and OIE don’t have powers to force compliance, and rely largely on advocacy. In 2011, 44 labs in 35 countries held stocks of rinderpest. Two years later, 28 labs in 23 countries held material. Now, 14 countries still hold some form of the virus, including the 6 that have designated facilities (see ‘Virus holdouts’). So far, Africa is the only region that has sequestered samples in a single facility, in Debre-Zeit, Ethiopia. The FAO and OIE keep the locations of labs holding the virus — apart from the designated facilities — secret because of concerns about bioterrorism and national security, says Lubroth.

The FAO and OIE launched the Sequence and Destroy project in 2015 — one of only two rinderpest research initiatives approved after a 2012 moratorium on studies was lifted in 2013. Sequence data is put into the public domain and could be used for forensic investigations into the origin of an outbreak in the case of a reintroduction. Should live virus be needed one day, researchers could also reconstruct strains from their whole genome sequences. The Pirbright Institute became the first to destroy stocks under the initiative in June. It got rid of around 3,500 vials of material representing some 50 strains and kept a small amount of live virus, says Michael Baron, who works on rinderpest at the institute.

A secure holding facility at the French Agricultural Research Centre for International Development (CIRAD) in Montpellier is organizing destruction of its samples, says CIRAD virologist Geneviève Libeau. It’s not yet clear whether the other designated rinderpest facilities — in Ethiopia, Japan, the United States and China — have firm plans to sequence and destroy their stocks.

Related virus

But authorities will hang on to some live rinderpest vaccines for use in an emergency. Baron’s research had explored whether the vaccine for the closely related peste des petits ruminants virus (PPRV) might also protect against rinderpest, because the rinderpest vaccine protects against PPRV. This would help with diagnostic measures needed in any rinderpest outbreak, and eliminate the need to retain stocks of live rinderpest vaccine. But tests reported in 2016 showed it didn’t1.

The FAO and the OIE now hope to eradicate PPRV by 2030. The virus kills millions of sheep and goats every year, the main livestock owned by some 300 million poor rural families in developing countries.

The experience of eradicating rinderpest and managing the post-eradication era will be invaluable, says Eloit. “Global freedom from a disease could be redefined as having destroyed all material and there being no holdings in laboratories or other facilities,” she says.

Nature 572, 18 (2019)

doi: 10.1038/d41586-019-02098-2

References

  1. 1.

    Holzer, B., Hodgson, S., Logan, N., Willett, B. & Baron, M. D. J. Virol. 90 5152–5162 (2016).

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